In recent decades, the age of heart transplant (HTX) recipients has been progressively increasing.1–3 This is because new drugs and devices for the treatment of heart failure (HF) have delayed the development of advanced HF at older ages.4,5 As a consequence, patients reach older ages in better physical and psychological condition. Moreover, greater knowledge of heart preservation and the vast amount of accumulated experience in transplantation has increased the use of hearts from older donors.6–8

Taking into account the age trend of donors and recipients described in the Spanish Heart Transplant Registry3 and in other annual registries,2,9,10 it would appear that there has been an increase in the implantation of younger hearts in older patients and vice versa. However, there is a knowledge gap regarding the frequency of these types of implantations, a lack of comparisons between the different groups (younger donor, older donor, younger recipient, older recipient) and between survival rates in these groups, and little information on the actual risk entailed by some of these combinations.

Our working hypothesis was that donor-recipient age combinations have a different impact on survival and that the worst combinations should be identified and possibly not used.

The objective of this study was to analyze the impact of donor-recipient age combinations on survival in HTX recipients.

We conducted a retrospective analysis of all transplants performed in Spain between January 1, 1993 and December 31, 2017. Pediatric transplants (under 16 years old), retransplants, and combined transplants (kidney, liver, or lung) were excluded. The final number of transplants was 6505 (figure 1).

Figure 1.

Patient selection algorithm. HTX, heart transplant.

(0.04MB).

The data analyzed were obtained from the Spanish Heart Transplant Registry, which includes all transplants performed in Spain (HTX is currently performed in 16 Spanish centers). Transplant data are prospectively entered into an online database. The registry includes more than 100 variables related to recipient, donor, intervention, immunosuppression, and follow-up (table 1 of the supplementary data. The Spanish Heart Transplant Registry is an official registry of the Spanish Ministry of Health and the Spanish Government. The appendix of the supplementary data shows the list of centers and collaborators of the Spanish Heart Transplant Registry. This subanalysis was approved by the Clinical Research Ethics Committee of the Hospital Universitari i Politècnic La Fe (Valencia, Spain).

An older recipient was defined as one more than or equal to 65 years. An older donor was defined as one more than or equal to 50 years. Four combinations were analyzed: younger donor-younger recipient (donor <50 years - recipient <65 years), younger donor-older recipient (donor <50 years - recipient ≥ 65 years), older donor-younger recipient (donor ≥ 50 years - recipient <65 years), and older donor-older recipient (donor ≥ 50 years - recipient ≥ 65 years). We also analyzed the predictive variables of mortality.

Variables are expressed as mean±standard deviation, or the median [interquartile range] in the absence of normality, and percentages. Differences between groups were analyzed using the chi-square test for qualitative variables and the Kruskal-Wallis test for quantitative variables. Survival curves were calculated using the Kaplan-Meier method and comparisons between them using the log-rank test. Cox proportional hazards model was used to adjust the multivariate model of donor-recipient age groups. In addition to the donor-recipient ages, we initially included variables of known clinical relevance and those that had a P value greater than 1 in the univariate analysis. Recipient age was included in the model via the combined donor-recipient age variable. Because recipient age is a categorical variable with more than 2 categories, its inclusion in the model entailed its transformation into dummy variables. A dummy variable is a dichotomous (binary) variable that can only take the value 0 or 1, indicating the absence or presence of a certain characteristic, respectively. The final model was obtained by using a backward procedure to simplify the nonsignificant variables included in the adjustment.

In the first decades of HTX, only people younger than 35 years were accepted as donors.11–13 However, as waiting lists grew and there was an urgent need for more hearts as soon as possible,14 transplant teams began to accept hearts from more donors.3,15,16 In addition, until relatively few years ago, HTX was exclusively restricted to recipients aged up to 50 years. However, in recent decades, the age of recipients has increased and the selection criteria have been expanded.1,17–19 These changes have been due to advances in surgical techniques, major improvements in postoperative treatment, and above all, new treatments and devices for HF that improve the quality and quantity of life, thus allowing these patients to reach older ages in good health.20,21 In addition, in recent decades, there has been progressive improvement in the treatment of diseases that may ultimately lead to ischemic HF (ie, the generalized use of primary angioplasty programs), valvular HF, cardiotoxicity, and so on. These improvements delay the onset and development of HF, thus shifting upward the age at which HTX is indicated. Therefore, since the beginning of HTX, donor and recipient age has also progressively increased. This trend may also be related to greater experience in THX. However, as of 2007, the progression curves separated and the proportion of donors older than 50 years increased annually much more than that of recipients older than 65 years. Thus, the annual proportion of donors older than 50 years old exceeded 50%. It is not clear what could have happened in that year, but it may have been the case that the greater demand due to longer waiting lists, the increase in urgent transplants, and more experience in donor selection led to the view that the older age of these donors was no longer considered to be an excessive risk to survival. Currently, all transplant teams accept donors above this age. The latest HTX register from the International Society for Heart and Lung Transplantation (ISHLT) also shows that from 2009 to 2017 there was a progressive increase in the age of donors.22

There are few scientific studies on the impact of this trend. Although the ISHLT guidelines recommended increasing the age of potential recipients to 70 years in 2006,23 many hospitals still consider age to be a limiting factor for HTX in patients with advanced HF. Data from the Spanish Heart Transplant Registry3 may clarify the relationship between donor-recipient age and survival. For all these reasons, this study analyzed the impact of 4 donor-recipient age combinations on HTX survival. The 4 groups comprised younger donor to younger/older recipient and older donor to a younger/older recipient. The results showed that there was a difference in survival between the 4 groups. The best combination was younger donor-younger recipient and the worst combination was older donor-older recipient. However, the results from other 2 groups are those with the greatest interest from the point of view of clinical practice.

We followed the previous literature to determine the cutoff point to consider a donor as older, because several studies have shown that a donor age of more than 50 years is associated with an increased risk of posttransplant mortality.7,24 Other studies have used cutoff points of 50 years or more and less than 40 years to consider donors as older and younger, respectively. Donors aged 40 to 49 years were excluded from the analyses to obtain a clearer distinction between the 2 groups.25 However, given the significant percentage of donors in this interval, we used a cutoff point of 50 years to include the entire spectrum of donors. Thus, the results of the analysis are more relevant from a clinical perspective and may assist in decision-making in real-world settings.

In Spain, 11% of patients who undergo HTX are older than 65 years. In these recipients, the most frequent cause of heart disease is of ischemic origin and the prevalence of comorbidities is higher; however, the proportion of urgent transplants and mechanical ventilation is lower. This profile is similar to that reported in previous studies, especially in relation to the higher prevalence of comorbidities and ischemic heart disease in this group of recipients. A steady trend (typically nonsignificant) has been observed toward a lower percentage of these patients undergoing urgent HTX.26

In the present study, 20% of the donors were older than 50 years and a higher percentage of women died from nontraumatic cerebrovascular causes. However, the recipient/donor weight ratio was better in the previous study.26 The aforementioned profile is similar to that reported in some registries,15,25 in which stroke was the most frequent cause of death in donors more than or equal to 50 years; however, the percentage of female donors in this group was not high.

The distribution of donor-recipient age groups shows that the number of patients differed in each group. The most frequent group was younger donor for younger recipient (73%) followed by older donor for younger recipient (16.2%). The Spanish Heart Transplant Registry3 database was used to obtain a sufficient number of patients in the less frequent groups (younger donor for older recipient [7.3%] and older donor for older recipient [3.5%]). This registry includes all the HTXs performed in Spain from the first one in May 1984 to the present and is completed by all the Spanish HTX teams.

Significant differences were found between transplants in older and younger recipients, with a difference of almost 3.5 years in median survival (12 years vs 8.7 years, respectively). An association was also found between an increase in the age of the recipients and a decrease in their probability of survival. In fact, in recipients older than 70 years, the probability of post-HTX 10-year survival was only 19.5%. However, there were no differences between recipient groups in early mortality. Thus, the survival curves were identical at the beginning and then began to gradually separate. This finding could be explained by expected survival time based on the age of the recipients independently of the transplant. It could also lead to the age of the recipient not being considered as the only criterion by which HTX could be contraindicated.

Differences were also found in median survival between donors and recipients older and younger than 50 years (11.8 years vs 10.3 years, respectively). In this case, however, the difference was 1.5 years. It therefore appears that donor age is not as relevant as recipient age as a cause of long-term mortality. The survival curve shows that the initial fall, which is related to the perioperative process, was greater when the donors were older. Subsequently, the curves tended to separate slightly, then from 5 years onward the separation clearly widened consistently over time. The scientific literature typically considers donor age to be an independent risk factor for mortality in HTX,27,28 although there are conflicting data. Data from the most recently published ISHLT registry11 and the United Network for Organ Sharing29 database show that advanced donor age increases the risk of mortality for all recipients. However, a Spanish study published in 2015 found no difference in mortality in older donors after adjusting for confounding factors, although it found a mid-term increase in the risk of vascular graft disease in older donors.

The present study found differences between donor-recipient age combinations. The worst mean survival time was found in the older donor-older recipient age combination (7.5 years). The other 3 combinations initially showed similar survival curves; however, from the fifth year onward the gap between curves began to widen. Thus, mean survival time was 12.1 years in the younger-younger combination, 10.5 years in the older-younger combination, and 9.1 years in the younger-older combination. The results show survival would be reduced in each risk combination by approximately 1.5 years in relation to the best combination (younger-younger, 12 years). A study published in 2020 assessed the relationship between donor and recipient age by dividing recipients into those younger than 60 years vs those older than or equal to 60 years and donors younger than 50 years vs those older than or equal to 50 years. Five-year survival was significantly lower among recipients who received an older heart than among those who received a younger heart (67% vs 73% respectively; log-rank test, P <.001).23

Multivariate analysis confirmed the relevance of donor-recipient age to survival. Thus, the risk of mortality was 32% higher in recipients older than 65 years than in recipients younger than 65 years. Furthermore, there were significant differences in survival between the best age combination (younger donor-younger recipient) and all the other combinations, except for one: there were no significant differences in survival between the older donor-younger recipient combination and the younger donor-younger recipient combination. This may make individuals older than or equal to 55 years suitable donors even for younger recipients without it being a predictor of worse survival. Furthermore, significance was maintained after adjustnebt if the variables with those that reached significance in the univariate analysis and that are known to be associated with posttransplant mortality.30,31 However, the option of transplanting older hearts into older patients (worst combination) should not be rejected, because in these patients survival times are much longer than those in patients older than 65 years with advanced HF.32,33

The results of the present study suggest that the age of the donor and recipient is a relevant prognostic factor in HTX. The donor-recipient age combination has prognostic implications that must be known and weighed up when accepting an organ for transplant.

None declared.